Adipose triglyceride lipase, also known as patatin-like phospholipase domain-containing protein 2 and ATGL, is an
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...
that in
human
Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, cultu ...
s is encoded by the ''PNPLA2''
gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
.
ATGL catalyses the first reaction of
lipolysis
Lipolysis is the metabolic pathway through which lipid triglycerides are hydrolyzed into a glycerol and free fatty acids. It is used to mobilize stored energy during fasting or exercise, and usually occurs in fat adipocytes. The most important ...
,
where
triacylglycerols are
hydrolysed
Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution, elimination, and solvation reactions in which water is the nucleophile.
Biological hydrolysis ...
to
diacylglycerols.
Properties
ATGL has very high
substrate specificity
Chemical specificity is the ability of binding site of a macromolecule (such as a protein) to bind specific ligands. The fewer ligands a protein can bind, the greater its specificity.
Specificity describes the strength of binding between a giv ...
for triacylglycerols. It contains a catalytic dyad using
serine-
aspartic acid.
Function
ATGL catalyses the first reaction of
lipolysis
Lipolysis is the metabolic pathway through which lipid triglycerides are hydrolyzed into a glycerol and free fatty acids. It is used to mobilize stored energy during fasting or exercise, and usually occurs in fat adipocytes. The most important ...
.
It
hydrolysis
Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution, elimination, and solvation reactions in which water is the nucleophile.
Biological hydrolys ...
triacylglycerols to
diacylglycerols by attacking the
fatty acid
In chemistry, particularly in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, ...
attached to carbon-3 of
glycerol
Glycerol (), also called glycerine in British English and glycerin in American English, is a simple triol compound. It is a colorless, odorless, viscous liquid that is sweet-tasting and non-toxic. The glycerol backbone is found in lipids known ...
.
ATGL acts as a control mechanism of lipolysis, as variations in diacylglycerol concentration impact enzymes in later stages of lipolysis.
Clinical significance
Defects in ATGL can cause problems in lipolysis, leading to
neutral lipid storage disease
Neutral lipid storage disease (also known as Chanarin–Dorfman syndrome) is a congenital autosomal recessive disorder characterized by accumulation of triglycerides in the cytoplasm of leukocytes (Jordan’s Anomaly) muscle, liver, fibroblasts, ...
.
As triacylglycerols are not hydrolysed to diacylglycerols, there is a build-up of triacylglycerol droplets in
granulocytes.
ATGL is regulated by insulin, and is similar to structure with adiponutrin, a protein that is regulated by nutrition. When there is a lack of insulin, there is an increased expression of the ATGL protein. Because adipose tissue triglyceride is a major form of energy storage, the study of how ATGL regulation and dysregulation can lead to potential problems will increase understanding of the pathophysiology behind metabolic disorders. ATGL is also the key enzyme that would be able to maintain a balance between mobilization and lipid storage. Lipolytic breakdown performed by ATGL would impact regulatory functions including but not limited to cell death, growth, signaling, metabolism, and gene expression.
References
Further reading
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External links
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{{Biochem-stub